tbuckley/cabot-search huggingface dataset:
P097: The status quo of involved-field radiotherapy – Quality analysis of radiotherapy in the GHSG HD 16
Authors: Michael Oertel, Dominik Hering, Christopher Kittel, Nina Nacke, Kai Kröger, Jan Kriz, Michael Fuchs, Christian Baues, Dirk Vordermark, Rita Engenhart-Cabillic, Klaus Herfarth, Peter Lukas, Heinz Schmidberger, Simone Marnitz, Peter Borchmann, Uwe Haverkamp, Andreas Engert, Hans Theodor Eich
Journal: HemaSphere (2022)

Question: The HD 16 trial of the German Hodgkin Study Group (GHSG) investigated the use of consolidative radiotherapy (RT) after 2 cycles of ABVD chemotherapy for early-stage Hodgkin lymphoma (HL) and could demonstrate the superiority of a combined modality approach [1]. The present work aims at analyzing the quality of involved-field RT used in this study. Methods/Material: For quality assessment, 100 randomly chosen plans from the HD 16 trial were requested and analyzed. RT was assessed by experts of the radiation therapy panel of the GHSG using initial (staging) imaging, RT plans and the recommendation forms by the reference radiation oncology. Evaluation was graded as „correct“, „minor deviation“ or „major deviation“. Statistical analyses were performed using SPSS (version 27/28, IBM, NY, USA). Results: Radiation doses were adequate with a median of 20 Gy (19.8 Gy-21.6 Gy) in normofractionation. In the majority of radiation series, supradiaphragmatic target volumes were treated (91 %), with the regions most commonly irradiated being supraclavicular left/right (73 % each), infraclavicular left/right (73 % each) and cervical left/right (44 % and 45 %, respectively). Acute treatment toxicities were mild to moderate with only 3 cases of grade 3–4 toxicities (1 nausea/vomiting, 1 dysphagia, 1 mucositis). According to the RT panel, 84 % of cases were evaluated as „correct“, 5 % as „minor deviations“ and 11 % as „major deviations“. Major deviations were caused by insufficient dose coverage of involved regions in most cases (10/11), predominantly in the upper mediastinum (5/10 cases). Previous GHSG studies in early-stage HL (HD 10 [2] and HD 13 [3]) showed lower rates of RT series according to protocol (38.8 % and 52 %, respectively). A χ2-test was used to compare the number of correct RT series in the different GHSG study generations (HD 13 vs. HD 16). No expected cell frequencies were below 5. Results reveal a significant improvement in favor of HD 16 (χ2(1)=33.8, p<0.001 Φ=-0.247). Similar outcomes were found for the association of GHSG study generation and the absence of major deviations (χ2(1)=27.4, p<0.001 Φ=- 0.222). Conclusion: Since its introduction in HD10, involved-field RT has evolved considerably. However, continuous efforts in RT quality assurance and training are needed in the modern era. Literature 1.JCO. November 2019; 37(31):2835-2845. 2.IJROBP. August 2008; 71 (5):1419-1424. 3.SUON. February 2017;193(2):109-115.
P081: Treatment-related circulatory diseases and mortality in Hodgkin lymphoma patients using multi-state modelling and relative survival
Authors: Joachim Baech, Lasse Hjort Jakobsen, Tarec Christoffer El-Galaly, Daniel Molin, Ingrid Glimelius, Joshua P. Entrop, Michael J. Crowther, Karin E. Smedby, Sandra Eloranta, Caroline E. Weibull
Journal: HemaSphere (2022)

Figure 1: Probability of: Alive with DCS-free (blue), excess DCS (green), expected DCS (light green), dead without DCS (red), dead with DCS (light red). Panel (a) contrasts men versus women. Panel (b) contrasts low versus high anthracycline dose (≤200/>200mg). Introduction: One of the most common late effects in Hodgkin lymphoma (HL) patients are diseases of the circulatory system (DCS). How much that can be attributed to HL therapy, while accounting for the competing risk of death, remains less understood. This study aimed to assess treatment-related incidence of DCS by sex and cumulative anthracycline dose in HL patients using novel methods in multi-state modelling and relative survival. Methods: All patients with HL registered in the Swedish Lymphoma Register 2000–2018, aged 18–80 years at diagnosis, were included. DCS was identified in the Swedish National Inpatient Register (ICD-10 codes I00-I99). Sex-, year-, and age-specific incidence rates of DCS in the general population were retrieved from public records. Patients were followed from treatment through a series of states: Alive without DCS, alive with DCS, dead without DCS, and dead after DCS. Follow-up ended on death, emigration, or December 31st, 2019. All state transitions were modelled separately using flexible parametric survival models. A relative survival model incorporating the expected DCS rates was fitted to allow for estimation of excess DCS incidence, which was defined as attributable to HL therapy. Transition probabilities were predicted for specific patient groups. Results: A total of 1,929 HL patients were included (54% male, 49% treated with >200 mg anthracycline). The distribution of treatments was 66% ABVD, 20% CHOP-like, and 14% BEACOPP. During a median follow-up time of 7.6 years, 377 patients (20%) were diagnosed with DCS, 145 (7.5%) died without DCS, and 87 (5%) died following DCS. Females had a lower non-DCS mortality rate than men (adj. hazard ratio=0.69, 95% CI: 0.49–0.97), as did patients treated with >200mg anthracycline compared to ≤200mg (adj. hazard ratio=0.28, 95% CI: 0.18–0.44). There were no differences in excess DCS incidence rates or post-DCS all-cause mortality rates. Figure 1a shows the predicted transition probabilities for an advanced stage patient diagnosed in 2000 at age 50, treated with ABVD including >200mg cumulative anthracycline dose, by sex. Figure 1b shows the transition probabilities for a limited stage male patient diagnosed in 2000 at age 50, treated with ABVD, by cumulative anthracycline dose (≤200mg or >200mg). Conclusion: Across almost two decades, females experienced more excess DCS compared to men, likely due to superior survival. The same was seen for high compared to low doses of anthracycline.
P076: Pneumococcal infection in splenectomised Hodgkin lymphoma patients: Do they pose a problem today and what is the best long-term strategy?
Authors: Magnus Björkholm, Caroline E. Weibull, Paul Dickman
Journal: HemaSphere (2022)

Purpose: Diagnostic laparotomy and splenectomy (DLS) were introduced for Hodgkin lymphoma (HL) patients in Sweden in the late 1960s/early-70s. It was soon established that splenectomised and functional hyposplenic (following irradiation) HL patients carried an increased risk of overwhelming infections, Streptococcus pneumoniae being the major causative agent. Despite this, DLS remained as a staging procedure for more than two decades. The purpose of this study was to compare incidence and outcome of pneumococcal infections between splenectomised (spl+) and non-splenectomised (spl-) HL patients. Material and Methods: HL patients diagnosed 1973–1995 were identified in the Swedish Cancer Register. Information on splenectomies and severe pneumococcal infections was retrieved from the National Inpatient Register. Follow-up started a diagnosis and ended on date of infection, emigration, death, or December 31, 2010, whichever came first. Splenectomy was analysed as a time-varying covariate, i.e., patients were considered unexposed before the date of splenectomy and exposed after the date of splenectomy. Cox proportional hazard models were used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs) comparing infection rates between spl+/spl- patients. Results: A total of 4,237 HL patients were included, among whom 735 (17%) underwent a splenectomy, with a median time from splenectomy to infection of 6.8 years (range 0.1–30.8 years). The number of patients experiencing a severe pneumococcal infection was 39 (3.2 per 1,000 person-years) among spl+ and 60 (1.7 per 1,000 person-years) among spl- patients. The relative rate of severe pneumococcal infection comparing spl+/spl- HL patients was 2.43 (95% CI: 1.55–3.81), adjusted for diagnosis year, diagnosis age, and sex. The 30-day post-infection mortality proportion was 9/39 (23%) among the spl+ and 18% (11/60) among the spl- patients. Broken down by calendar period of infection, the 30-day post-infection mortality proportion among splenectomised patients was 44% (1973–1985), 23% (1986–1998), and 0% (1999–2010). Conclusion: Severe pneumococcal disease is a serious event that is more likely to appear in splenectomised HL patients compared to non-splenectomised, possibly many years after diagnosis. However, the low proportion of deaths in later decades is reassuring, and likely a result of adequate pneumococcal vaccination together with patient and doctor education about the infection risk.
P069: Characterisation of influencing parameters on oocyte quality preservation in a cohort of Hodgkin lymphoma patients
Authors: Chloé Chuzel, Virginie Simon, Hélène Béhal, Franck Morschhauser, Christine Decanter, Morgane Nudel
Journal: HemaSphere (2022)

Background: Hodgkin lymphoma (HL) is the most frequent lymphoma in the young population. The standard of treatment is chemotherapy including alkylating agents known to affect fertility. Fertility preservation is usually proposed before treatment with oocyte cryopreservation as a reference. In different cohorts of healthy women, some factors are well known to have an impact on oocyte quality preservation such as age, anti-Müllerian hormone (AMH), body mass index (BMI). German Hodgkin Study Group (GHSG) distinguishes 3 prognostic groups: early, intermediate, advanced stages (respectively defined GHSG I, II, III in our study). In literature, the parameters influencing fertility preservation outcomes in HL are not clear, namely HL’s stage and inflammation. In this study we evaluated the impact of HL’s stage using GHSG criteria on fertility preservation outcomes. Methods: We performed a retrospective study on 79 women, with newly diagnosed and previously untreated HL who underwent oocyte cryopreservation between 2012 and 2021. The patients were extracted from a cohort of fertility observatory in Lille University Hospital. The primary outcome was the number of metaphase 2 oocyte retrieved (M2). Estradiol level at the ovulation induction and the ratio of M2/follicles >15mm were secondary outcomes. We compared fertility outcomes between two groups: early and intermediate stage (GHSG I+II) and advanced stage (GHSG III). We evaluated in univariate and multivariate analyses the following factors: AMH, BMI, use of hormonal contraception, age and C reactive protein (CRP). Results: The two groups (GHSG I-II and GHSG III) were comparable. In univariate analyses, AMH was the only statistically significant factor regarding the number of M2 (p<0,0001) and Estradiol level (p<0,0001). In multivariate analysis, GHSG score was not statistically significant concerning Estradiol level (p=0,5) contrary to AMH level (p<0,0001). Conclusion: In our study, AMH level is doubtlessly a factor impacting the quality of oocyte preservation. HL’s stage and inflammation do not seem to affect fertility preservation outcomes in the whole cohort. These results, based on the largest cohort of HL patients evaluating HL’s risk groups provide important information about expected cryopreservation outcomes. According to this study, oocyte cryopreservation should be considered even for patients with advanced HL’s stage.
P068: A Retrospective Analysis of Fertility in Female Patients with Advanced Stages of Hodgkin Lymphoma Treated with BEACOPP Escalated Chemotherapy (25 Year Experience of a Single Centre)
Authors: Jana Marková, Heidi Mociková, Lubica Gaherová, Katerina Klásková, Maria Maco, Katerina Dedeckova, Tomas Kozak
Journal: HemaSphere (2022)

Background: BEACOPP escalated (eBEA) includes alkylating agents and its gonadal toxicity has been reported in prospective and retrospective studies. This retrospective study analyzed fertility of 119 young female patients (pts) with initial diagnosis of Hodgkin lymphoma (HL) in advanced stages treated with eBEA. Patients and Methods: Overall 128 women aged 18–34 years (median age at diagnosis was 27 years) were treated with eBEA between 1997 and 2020. Median follow-up since the beginning of the treatment was 12.4 years. Overall 57 pts (48%) received 8 cycles of eBEA, 46 pts (39%) were treated wit 6 cycles and 16 pts (13%) received 4 cycles of eBEA. Additional radiotherapy was indicated in 36 pts (30%). Gonadotropin-releasing hormone-analogue Gosereline acetat received 68 pts (57%) and 51(43%) pts used oral contraceptives during chemotherapy to prevent gonadal toxicity. Median follow-up after the end of treatment was 12 years. Results: Out of 119 women 45 (38%) delivered 61 babies including 18 (40%) women with 2 deliveries after treatment with eBEA. Number of all delivered healthy babies was 59 (one baby was born with small cleft lip, other with mild renal malformation). Two pregnancies were terminated prematurely (week 20 and 22) due to congenital malformations: monozomy 45, X0 Turner syndrome and serious cleft lip). All pregnancies were spontaneous except of 6 women that underwent in vitro fertilisation (IVF) Median time from the end of terapy until the delivery of the first baby was 66 months (range 18-169m). 40 children (65%) were born in the group of pts aged 18–24 years, 16 (26%) in the group of 25–29 years and only 5 (9%) in the group of 30–34 years. Conclusion: Our data indicate that even after eBEA 38% of young fertile women in advanced stages of HL are able to deliver babies and protection of fertility should be offered to them. Implementation of new strategies with reduction of chemotherapy cycles based on PET may further contribute to fertility preservation.
P055: Validation of the tumor cell-specific rearranged IgG-encoding circulating cell-free DNA for the treatment response monitoring in patients with classic Hodgkin lymphoma
Authors: Ilia Buhtoiarov, Brian Hill, Ilan Kirsch, Nancy Richter, Rabi Hanna
Journal: HemaSphere (2022)

Table 1: Clinical characteristics of patients Background: Detection and longitudinal monitoring of the cell-free circulating tumor-specific DNA (ctDNA) in plasma of cancer patients is a potent tool for treatment response assessment and detection of the early disease recurrence. There is a number of the next-generation sequencing (NGS) panels for analysis of the commonly mutated genes in tumors of classic Hodgkin lymphoma (cHL) patients, which are being validated for clinical use. The Cleveland Clinic team, in collaboration with Adaptive Biotechnologies, is exploring if longitudinal assessment of ctDNA encoding the patient- and tumor cell-specific rearranged heavy or light (kappa/lambda) chain IgG (r-IgH/r-IgK/L, could be used for the treatment response and early recurrence monitoring in cHL patients. Methods: Enrolled are patients (9–99 y) with newly diagnosed and previously untreated cHL. First, the diagnostic biopsy specimen and the pre-treatment plasma are tested for concordant presence of dominant r-IgH/r- IgK/L ctDNA sequences. Sequence dominance and suitability for tracking is determined according to the Adaptive Biotechnologies’ diagnostic algorithm validated for other B cell neoplasms. If dominant r-IgH/r-IgK/L sequence(s) is detected, the patient plasma is serially tested during and following completion of therapy. Results: Pilot results on first 4 patients are presented. Patients’ clinical characteristics are summarized in Table 1. P1 had a single dominant r-IgH ctDNA sequence; P2 had two dominant r-IgH ctDNA sequences; P3 had two r-IgH and one dominant IgK ctDNA sequences; the latter was chosen for serial tracking; P4 had a single dominant r-IgH ctDNA sequence. In P1 and P2, the concentration of ctDNA precipitously declined below detectable threshold following completion of the first two cycles of therapy, and remained undetectable through the end of treatment. These laboratory changes correlated well with the treatment response assessed by functional imaging. For P2 and P3, the in-treatment samples are in process of acquisition. Conclusion: The preliminary results of this pilot project demonstrate feasibility of establishing trackable ctDNA sequences encoding IgG heavy or light chain, with intra- and interpatient clonotypic heterogeneity of the dominant sequences. Correlation between results of the functional imaging treatment assessment and detectable quantity of ctDNA in plasma was observed. Further testing is underway.
P096: Polymorphisms in SETD7 may predispose the risk of developing late cardiac side effects after radiotherapy including the mediastinum in Hodgkin’ s lymphoma.
Authors: Johan Linderoth, Eva Freyhult, Ellinor Andreasson, Ann-Sofie Johansson, Anne Andersson, Ingrid Glimelius, Gunilla Enblad, Daniel Molin
Journal: HemaSphere (2022)

Background: In Hodgkin’s lymphoma (HL) radiation therapy including the mediastinum is known to cause long time cardiac side effects. Method: A cohort of 183 previous HL patients who received radiotherapy involving the mediastinum during the period of 1965–1995 were dichotomized into patients with or without known cardiac complications. This was done after a separate study visit performed with a range of 13–43 years from diagnosis (median 23 years). A complication was defined as having a medical record of any of the following clinical conditions: angina, myocardial infarction, congestive heart failure or valvular disease. DNA was extracted from whole blood and analyzed using Infinum OncoArray-500K. We analyzed a set of 4341 single nucleotide polymorphisms (SNPs) representing 167 genes previously associated with late side effects of radiotherapy or associated with the normal myocyte function, ischemic heart disease, primary restrictive cardiomyopathy or valvular disease. The association between cardiac status and alterations in SNPs was examined. Forty-six of the patients had also received doxorubicin, an anthracycline associated with late cardiotoxic side effects. Results: A SNP of SETD7 (intron), rs2725790, significantly differed between the two groups (allelic test, p = 9.2E-6, maxT permutation test p=0.024, logistic regression p=0.00013). To take prior anthracycline therapy into account, logistic regression was performed adjusting for anthracycline therapy (logistic regression p=0.00020). Conclusion: This study indicates that constitutional differences in SETD7, a gene associated with epigenetic regulation of cardiomyogenesis and response to cardiac hypoxia may be involved in the risk of developing late cardiac side effect after radiation therapy of the mediastinum in the treatment of HL.
T066: Treatment and sex-specific exposure-based risk-stratification for care of survivors of childhood Hodgkin Lymphoma: A report from the Childhood Cancer Survivor Study
Authors: Michaela Dinan, Kayla Stratton, Wendy Leisenring, Yutaka Yasui, Eric Chow, Emily Tonorezos, Chaya Moskowitz, Jennifer Yeh, David Noyd, Gregory Armstrong, Kevin Oeffinger
Journal: HemaSphere (2022)

Figure 1: Cumulative grade 3–5 toxicity-free survival in A) females and B) males treated for pediatric Hodgkin Lymphoma in patients with high risk (grey line) and medium risk (red line) treatment exposures and their matched siblings (blue line). Background: Investigators from the United Kingdom (UK) have previously developed a treatment exposure-based algorithm that stratifies pediatric cancer survivors into low, medium, and high-risk groups. We sought to use the large, diverse population of the Childhood Cancer Survivor Study (CCSS) to validate risk for poor outcomes in children treated for Hodgkin Lymphoma with an emphasis on the impact of sex on long term outcomes. Methods: Five-year survivors of childhood cancer (diagnosed between 1970–1999 at <21 years of age) were categorized into medium and high-risk groups based on treatment exposures and diagnoses. High risk was defined by receipt of transplant, doxorubicin equivalent dose ≥ 250, or direct radiation to the neck, chest, abdomen, or pelvis. The primary endpoint included cumulative incidence of grade 3–5 chronic conditions (CTCAEv4.03) conditional on reaching age 25 without the outcome. Patients were censored at age 40 and siblings used as a comparison group. Cox proportional hazards models estimated hazard ratios (HRs) and 95% confidence intervals (CI) of new onset grade 3–5 conditions adjusted for sex and race. Results: A total of 2,131 survivors of Hodgkin Lymphoma met study criteria with a median follow-up of 22 years and median age of 36 at last follow-up. Using the above criteria, the final cohort included 241 medium and 1,890 high risk survivors. Among those who survived to age 25 without any grade 3–5 conditions, the risk of developing one by age 40 was 39.8% (95% CI 37.2–42.5%) for high risk patients and 27.2% (19.8–37.2%) for medium risk patients, respectively, and 8.5% (7.5–9.7%) for siblings. The risk of grade 3–5 condition by age 40 in high risk patients was substantially higher for females at 50.6% (46.9–54.6) than for males at 29.7% (26.6–33.3%). In multivariable analysis the strongest predictor of grade 3–5 conditions remained female vs. male sex (HR 1.9, 95% CI 1.6–2.3), followed by high vs. medium risk (HR 1.7, 95% CI 1.2–2.4). Toxicity was not associated with race. Conclusions: Females treated for childhood Hodgkin Lymphoma remained at nearly double the risk of long-term high grade toxicity compared to males after adjusting for treatment exposures. Patient sex may help supplement standardized risk assessment of Hodgkin Lymphoma survivors and help inform physicians attempting to determine follow-up intervals, management, and long-term surveillance of these survivors.
P075: My Hodgkin, My Health: Feasibility of a mobile application to collect long term follow up data about Hodgkin patients
Authors: Gajan Kailainathan, Janlyn Falconer, Amy Baker, Nicole Wong Doo, Judith Trotman
Journal: HemaSphere (2022)

Background: There is increasing utility of novel agents in the treatment of Hodgkin lymphoma (HL) and the role of radiotherapy is evolving. Whilst there is a large body of research into the long-term outcomes of HL, this data is mostly related to conventional radiotherapy and chemotherapy regimens. With the advent novel therapies, our understanding of the long-term toxicities is also undergoing a period of dynamic change. Whilst recent trials provided abundant high-level short term follow up data, they fail to provide a full picture of the long-term morbidity and mortality associated with current therapy. The My Hodgkin, My Health (MHMH) app will be the first designed to collect patient derived data from HL patients. The purpose of this study is to demonstrate feasibility of this novel construct by meeting pre-specified recruitment and retention targets. Given the good overall survival of HL, and the paucity of long-term data in an era of novel therapies, we feel this is the ideal space in which to develop this app to capture this data conveniently and economically. Methods: This will be a pilot study to with Initial recruitment targeted at Australian participants of the RATHL study. This is a well-defined population who are familiar with study procedures and well connected with investigators who will disseminate recruitment information. To prove feasibility, the primary outcome of this study is to recruit ≥50% of Australian RATHL study participants and retain ≥ 50% of these participants at 12 months. Secondary endpoints will include disease status and relapse rates, fertility, and other long-term sequelae from HL treatment. Screening and consent procedures will be done electronically. Subjects complete a baseline survey including details of their treatment and disease status as well as information about any treatment complications. Subjects will be encouraged to update their data and be prompted to save or update their data every 6 months through push notifications. If the primary endpoint is met, the project will continue with a focus on the secondary endpoints. We also envisage collaboration with international investigators and global uptake of the app. Ideally MHMH will be an invaluable database for researchers moving forward and will facilitate clinical trials aimed at optimising treatment efficacy whilst balancing quality of life and treatment sequelae.